Essence of the Giant Reduction of Power Density in Osmotic Energy Conversion in Porous Membranes: Importance of Testing Area.

Harvesting osmotic energy through nanofluidic devices with diverse materials has received considerable attention in recent years. Often, a small testing area on a membrane was chosen to assess its power performance by calculating power density as output power per effective area. Since the choice of this testing area is arbitrary, and it is usually quite small, the result obtained can be too optimistic. There is a need to come up with a common standard so that the performance of a device/membrane can be assessed reasonably. In this study, we systematically investigate the power density as a function of testing area in nanoporous anodic-aluminum-oxide membranes. Through changing the aperture size of substrates, we clearly show that the obtained power density decreases drastically with increasing testing area. For instance, the power density acquired from the testing area of µm2-scale can be five orders of magnitude larger than that from the pristine membrane of cm2-scale. We also advance simulations by building a 3D model to simulate osmotic-driven ion transport in the multichannel system. The result of modeling agrees with our experimental observation that the power density decreases with increasing number of channels, and the ionic concentration profile reveals that the concentration polarization becomes serious as the number of channels increases. Our result highlights the importance of effective area on testing the power performance in nanofluidic devices.

An experimental model for ovarian cancer: propagation of ovarian cancer initiating cells and generation of ovarian cancer organoids.

BACKGROUND: Ovarian cancer (OC) is the most lethal gynecological cancer due to the recurrence of drug-resistance. Cancer initiating cells (CICs) are proposed to be responsible for the aggressiveness of OC. The rarity and difficulty of in vitro long-term cultivation of CICs challenge the development of CIC-targeting therapeutics. Reprogramming cancer cells into induced cancer initiating cell (iCICs) could be an approach to solve these. Several inducible CICs have been acquired by activating the expression of stemness genes in different cancer cells. However, few reports have demonstrated the feasibility in OC. METHODS: Patients with primary OC receiving surgery were enrolled. Tumor tissue were collected, and OCT4, SOX2, and NANOG expressions were assessed by immunohistochemistry (IHC) staining to investigate the association of stemness markers with overall survival (OS). An high-grade serous ovarian cancer (HGSOC) cell line, OVCAR-3 was reprogrammed by transducing Yamanaka four factors OCT4, SOX2, KLF4 and MYC (OSKM) to establish an iOCIC model, iOVCAR-3-OSKM. CIC characteristics of iOVCAR-3-OSKM were evaluated by RT-PCR, sphere formation assay and animal experiments. Drug-resistance and migration ability were accessed by dye-efflux activity assay, MTT assay and migration assay. Gene profile was presented through RNA-sequencing. Lineage differentiation ability and organoid culture were determined by in vitro differentiation assays. RESULTS: In OC patients, the co-expression of multiple stem-related transcription factors (OCT4, SOX2, and NANOG) was associated with worse OS. iOVCAR-3-OSKM cells generated by reprogramming successfully exhibited stemness characteristics with strong sphere-forming and tumorigenesis ability. iOVCAR-3-OSKM cells also showed malignant potential with higher drug resistance to chemodrug, Paclitaxel (PTX) and migration ability. iOVCAR-3-OSKM was maintainable and expandable on feeder-dependent culture condition, it also preserved ovarian lineage differentiation abilities, which could well differentiate into OC cells with CK-7 and CA125 expressions and develop into an organoid mimic poor prognostic OC histological feature. CONCLUSIONS: The establishment of iOVCAR-3-OSKM not only allows us to fill the gap in the information on induced CICs in OC but also provides a potential strategy to develop personalized CICs and organoid models for treating OC in the near future.

A DNA Damage Response Gene Panel for Different Histologic Types of Epithelial Ovarian Carcinomas and Their Outcomes.

DNA damage response (DDR) is important for maintaining genomic integrity of the cell. Aberrant DDR pathways lead to accumulation of DNA damage, genomic instability and malignant transformations. Gene mutations have been proven to be associated with epithelial ovarian cancer, and the majority of the literature has focused on BRCA. In this study, we investigated the somatic mutation of DNA damage response genes in epithelial ovarian cancer patients using a multiple-gene panel with next-generation sequencing. In all, 69 serous, 39 endometrioid and 64 clear cell carcinoma patients were enrolled. Serous carcinoma patients (69.6%) had higher percentages of DDR gene mutations compared with patients with endometrioid (33.3%) and clear cell carcinoma (26.6%) (p < 0.001, chi-squared test). The percentages of DDR gene mutations in patients with recurrence (53.9 vs. 32.9% p = 0.006, chi-squared test) or cancer-related death (59.2 vs. 34.4% p = 0.001, chi-squared test) were higher than those without recurrence or living patients. In endometrioid carcinoma, patients with ≥2 DDR gene mutations had shorter PFS (p = 0.0035, log-rank test) and OS (p = 0.015, log-rank test) than those with one mutation or none. In clear cell carcinoma, patients with ≥2 DDR gene mutations had significantly shorter PFS (p = 0.0056, log-rank test) and OS (p = 0.0046, log-rank test) than those with 1 DDR mutation or none. In the EOC patients, somatic DDR gene mutations were associated with advanced-stage tumor recurrence and tumor-related death. Type I EOC patients with DDR mutations had an unfavorable prognosis, especially for clear cell carcinoma.

Factors Influencing the Discordancy Between Intraoperative Frozen Sections and Final Paraffin Pathologies in Ovarian Tumors.

AIM: To retrospectively investigate the pre-operative clinical factors and ultrasonographic features that influence the accuracy of the intraoperative frozen section (IFS) of ovarian tumors. PATIENTS AND METHODS: Women with ovarian tumors that underwent IFS in one tertiary medical center were recruited from January 2010 to December 2018. Demographic and clinical data of these women were retrieved from medical records in the hospital's centralized database. RESULTS: A total of 903 ovarian tumors were enrolled, including 237 (26.2%) benign, 150 (16.6%) borderline tumor, and 516 (57.2%) malignant. The overall accuracy of IFS among all specimens was 89.9%. The sensitivities of IFS in diagnosing borderline tumors (82.0%) and malignant tumors (88.2%) were lower than in diagnosing benign tumors (98.7%, p <0.001, Z-test). The specificity of diagnosing malignant tumors (99.7%) was significantly higher than that of diagnosing benign tumors (94.7%, p <0.001, Z-test). The group with discordant IFS and final paraffin pathology (FPP) had younger age (47.2 ± 14.0 vs. 51.5 ± 11.8 years, p = 0.013, Mann-Whitney U test), and higher percentage of early-stage disease (85.2% vs. 65.1%, p = 0.001, chi-square test) and mucinous (39.3% vs. 3.3%) and endometrioid histologic types (34.4% vs. 20.2%) than the concordant group (all by chi-square test). Menopause (OR 0.34, 95% CI 0.15-0.76, p = 0.009), multicystic tumor in ultrasound (OR 2.14, 95% CI 1.14-4.01, p = 0.018), and ascites existence (OR 0.33, 95% CI 0.14-0.82, p = 0.016) were factors related to the discordant IFS by multivariate analysis. CONCLUSIONS: IFS has good accuracy in the diagnosis of ovarian tumors. We recommend more frozen tissue sampling for sonographic multicystic tumors in premenopausal women to improve the accuracy of IFS.

High prevalence of APOA1/C3/A4/A5 alterations in luminal breast cancers among young women in East Asia.

In East Asia, the breast cancer incidence rate among women aged <50 years has rapidly increased. Emerging tumors are distinctly characterized by a high prevalence of estrogen receptor (ER)-positive/human epidermal growth factor receptor (HER2)-negative cancer. In the present study, we identified unique genetic alterations in these emerging tumors. We analyzed gene copy number variations (CNVs) in breast tumors from 120 Taiwanese patients, and obtained public datasets of CNV and gene expression (GE). The data regarding CNV and GE were separately compared between East Asian and Western patients, and the overlapping genes identified in the comparisons were explored to identify the gene-gene interaction networks. In the age <50 years/ER + /HER2- subgroup, tumors of East Asian patients exhibited a higher frequency of copy number loss in APOA1/C3/A4/A5, a lipid-metabolizing gene cluster (33 vs. 10%, P < .001) and lower APOA1/C3/A4/A5 expressions than tumors of Western patients. These copy number loss related- and GE-related results were validated in another Taiwanese cohort and in two GE datasets, respectively. The copy number loss was significantly associated with poor survival among Western patients, but not among East Asian patients. Lower APOA1, APOC3, and APOA5 expressions were associated with higher ESTIMATE immune scores, indicating an abundance of tumor-infiltrating immune cells. In conclusion, APOA1/C3/A4/A5 copy number loss was more prevalent in luminal breast tumors among East Asian women aged <50 years, and its immunomodulatory effect on the tumor microenvironment possibly plays various roles in the tumor biology of East Asian patients.

Seroprevalence Surveys for Anti-SARS-CoV-2 Antibody in Different Populations in Taiwan With Low Incidence of COVID-19 in 2020 and Severe Outbreaks of SARS in 2003.

Accurate detection of anti-SARS-CoV-2 antibodies provides a more accurate estimation of incident cases, epidemic dynamics, and risk of community transmission. We conducted a cross-sectional seroprevalence study specifically targeting different populations to examine the performance of pandemic control in Taiwan: symptomatic patients with epidemiological risk and negative qRT-PCR test (Group P), frontline healthcare workers (Group H), healthy adult citizens (Group C), and participants with prior virologically-confirmed severe acute respiratory syndrome (SARS) infection in 2003 (Group S). The presence of anti-SARS-CoV-2 total and IgG antibodies in all participants were determined by Roche Elecsys® Anti-SARS-CoV-2 test and Abbott SARS-CoV-2 IgG assay, respectively. Sera that showed positive results by the two chemiluminescent immunoassays were further tested by three anti-SARS-CoV-2 lateral flow immunoassays and line immunoassay (MIKROGEN recomLine SARS-CoV-2 IgG). Between June 29 and July 25, 2020, sera of 2,115 participates, including 499 Group P participants, 464 Group H participants, 1,142 Group C participants, and 10 Group S participants, were tested. After excluding six false-positive samples, SARS-CoV-2 seroprevalence were 0.4, 0, and 0% in Groups P, H, and C, respectively. Cross-reactivity with SARS-CoV-2 antibodies was observed in 80.0% of recovered SARS participants. Our study showed that rigorous exclusion of false-positive testing results is imperative for an accurate estimate of seroprevalence in countries with previous SARS outbreak and low COVID-19 prevalence. The overall SARS-CoV-2 seroprevalence was extremely low among populations of different exposure risk of contracting SARS-CoV-2 in Taiwan, supporting the importance of integrated countermeasures in containing the spread of SARS-CoV-2 before effective COVID-19 vaccines available.

Clinical factors associated with prognosis in low-grade serous ovarian carcinoma: experiences at two large academic institutions in Korea and Taiwan.

Low-grade ovarian serous carcinoma (LGSOC) has clinical features different from high-grade serous ovarian carcinoma (HGSOC) accounting for the majority of epithelial ovarian cancer. Because of its rarity, previous studies have only focused on the high-grade disease without considering the differences between the two subtypes. This study aimed to evaluate the effect of the clinical prognostic factors known for HGSOC on survival in patients with LGSOC. Based on the Federation of Gynecology and Obstetrics (FIGO) stage, progression-free survival (PFS) was markedly decreased in advanced disease compared with early disease. For stage I, patients with stage IC had poorer survival than those with stage IA and IB regardless of the number of cycles of adjuvant chemotherapy. For advanced disease, no gross residual disease after primary cytoreductive surgery was significantly associated with longer PFS when compared with gross residual disease. In multivariate analysis for PFS and overall survival (OS), age, preoperative CA-125, time interval from surgery to chemotherapy, and the number of cycles of adjuvant chemotherapy were not associated with prognosis. Complete cytoreduction was the only independent prognostic factor for PFS (HR 2.45, p = 0.045). Our study revealed that the known prognostic factors in HGSOC did not show any effect on the survival in LGSOC except for FIGO stage and complete cytoreduction.

Novel monoclonal antibody against integrin α3 shows therapeutic potential for ovarian cancer.

Ovarian cancer has a high recurrence rate after platinum-based chemotherapy. To improve the treatment of ovarian cancer and identify ovarian cancer-specific antibodies, we immunized mice with the human ovarian carcinoma cell line, SKOV-3, and generated hybridoma clones. Several rounds of screening yielded 30 monoclonal antibodies (mAbs) with no cross-reactivity to normal cells. Among these mAbs, OV-Ab 30-7 was found to target integrin α3 and upregulate p53 and p21, while stimulating the apoptosis of cancer cells. We further found that binding of integrin α3 by OV-Ab 30-7 impaired laminin-induced focal adhesion kinase phosphorylation. The mAb alone or in combination with carboplatin and paclitaxel inhibited tumor progression and prolonged survival of tumor-bearing mice. Moreover, immunohistochemical staining of ovarian patient specimens revealed higher levels of integrin α3 in cancer cells compared with normal cells. By querying online clinical databases, we found that elevated ITGA3 expression in ovarian cancer is associated with poor prognosis. Taken together, our data suggest that the novel mAb, OV-Ab 30-7, may be considered as a potential therapeutic for ovarian cancer.

Electrophysiological parameters that contribute to the pathogenesis of familial amyloid polyneuropathy caused by transthyretin mutations.

Familial amyloid polyneuropathy (FAP) is a rare, hereditary peripheral neuropathy commonly caused by mutations in human transthyretin (TTR) gene. Clinically, FAP caused by TTR mutations (TTR-FAP) involves both large and small nerve fibers. Details of early electrophysiological features in TTR-FAP remain unclear. To address this issue, we evaluated nerve excitability (NET) results in motor axons of control mice and two transgenic mouse models carrying V30M (TTRV30M) or A97S (TTRA97S) mutations that simulate clinical features of TTR-FAP. Transgenic TTRV30M and TTRA97S mice demonstrated significant increases in latency in hindlimb withdraw tests, as well as, poor rotarod test performance, compared to TTRORF mice. NET evaluation showed reduced S2 accommodation, and increased TEdundershoot during threshold electrotonus (TE) in motor axons of both TTRV30M and TTRA97S mice, indicating that axonal membranes were in a depolarized state. Decreased rheobase combined with increased refractoriness in the transgenic mice suggested that there were reduced sodium currents. Further immunohistochemical study of the sciatic nerves revealed the significantly decrease of voltage-gated sodium channel expression in the transgenic mice. Moreover, superexcitability during the recovery cycle is significantly increased in transgenic mice compared with control mice, which is attributed to increased internodal capacitance. Finally, the electron microscopy demonstrated the reduced g-ratio in TTRA97S mice may correlate with an atrophic change of axons and/or increase of myelin thickness. In summary, we evaluated NET results in transgenic mice which modeled the clinical features presented in TTR-FAP patients. Reduced sodium channel expression and increased internodal capacitance are factors contributing to the electrophysiological changes in TTR-FAP.

Frequent CTNNB1 or PIK3CA Mutations Occurred in Endometrial Endometrioid Adenocarcinoma With High Levels of Microsatellite Instability and Loss of MSH2/MSH6 Expression.

BACKGROUND: DNA mismatch repair (MMR) proteins form 2 heterodimers-MutSα formed by MSH2 and MSH6, and MutLα by MLH1 and PMS2. In endometrial endometrioid adenocarcinomas, cases with MMR protein defect also usually harbor other recurrent genetic mutations of the neoplasm. However, it remains unknown whether defects of the 2 functionally different heterodimers are linked to mutations in different genes. We aimed to study the MMR protein expression, microsatellite instability (MSI), and other common genetic mutations of endometrial endometrioid adenocarcinoma. MATERIALS AND METHODS: We investigated the MSI status of 107 endometrial endometrioid adenocarcinoma patients. MMR protein expression, and mutation of KRAS, CTNNB1, and PIK3CA were also evaluated by immunohistochemistry and sequencing. RESULTS: An overall 34.6% (37/107) of endometrial endometrioid adenocarcinomas were MSI-H. All MSI-H tumors exhibited loss of MMR protein expression (loss of MLH1, PMS2, MSH6, and MSH2 was noted in 22, 25, 12, and 7 cases, respectively). CTNNB1, PIK3CA, and KRAS mutation were present in 9, 7, and 7 MSI-H tumors. Compared with patients with loss of PMS2 and/or MLH1 expression, patients with loss of MSH6 and/or MSH2 expression were associated with higher frequencies of CTNNB1 mutation (P=0.036) and PIK3CA mutation (P=0.025). CONCLUSIONS: In MSI-H endometrial endometrioid adenocarcinomas, different types of MMR protein deficiency indicate different molecular genetic alterations.

Mosaic paternal haploidy in a patient with pancreatoblastoma and Beckwith-Wiedemann spectrum.

Pancreatoblastoma is a rare type of pancreatic cancer in children. Here, we describe a case in which Beckwith-Wiedemann syndrome (BWS) was first suspected because of placental mesenchymal dysplasia. Although the baby did not show the stigmata characteristic of BWS or abnormal peripheral blood methylation, she developed a massive pancreatoblastoma 2 months later. She survived after partial excision of the tumor and chemotherapy. The methylation pattern of the pancreatoblastoma tissue was typical of BWS. Single nucleotide polymorphism (SNP) array analyzes revealed that the pancreatoblastoma tissue had genome-wide loss of maternal alleles. Peripheral blood and nontumor pancreatic tissue showed normal biparental genomic contribution. Interphase fluorescence in situ hybridization analysis with centromeric probes for chromosomes 2 and 11 revealed haploid pancreatoblastoma cells, whereas the placental mesenchymal dysplasia tissue and nontumor pancreas tissue showed diploidy. SNP genotype analysis suggested the presence of mosaicism with the pancreatoblastoma tissue having a different paternal haplotype than that of the peripheral blood and nontumor pancreatic tissue. We report for the first time mosaic paternal haploidy associated with pancreatoblastoma. Babies with placental mesenchymal dysplasia, even those without a definitive diagnosis of BWS, need to be closely followed for the occurrence of embryonic tumors.

Differences in the association between glycemia and uric acid levels in diabetic and non-diabetic populations.

AIMS: Our study aimed to investigate the influence of different glycemic statuses and their fasting plasma glucose/2-hour post-load glucose on uric acid level. METHODS: A total of 14,787 subjects were recruited after excluding subjects with medication for hyperuricemia or diabetes. Fasting plasma glucose (FPG), 2-hour post-load glucose (2hPG), and uric acid (UA) were measured. Then, subjects were divided into normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes. RESULTS: After adjustment for clinical variables, in NGT group, there was no significant relationship found between UA level and FPG. However, there was a positive association between UA level and 2hPG (ß = 0.003, 95% CI: 0.002~0.004). A similar trend was also observed between UA level and 2hPG in IFG group (ß = 0.004, 95% CI: 0.000~0.009) and IGT group (ß = 0.005, 95% CI: 0.002~0.008), but relationship between UA level and FPG remained insignificant. In diabetes group, UA level was negatively associated with both FPG (ß = -0.008, 95% CI: -0.010 ~ -0.007) and 2hPG (ß = -0.005, 95% CI: -0.006 ~-0.003). CONCLUSIONS: In non-diabetic individuals, UA level increased with 2hPG, but not with FPG, and UA level was inversely associated with both FPG and 2hPG in diabetic population.

IgG4-related Ophthalmic Disease in Idiopathic Sclerosing and Non-Sclerosing Orbital Inflammation: A 25-Year Experience.

Purpose: To determine the prevalence, clinical manifestations, and treatment outcomes of IgG4-related ophthalmic disease (IgG4-ROD) in previously diagnosed idiopathic orbital inflammation (IOI).Materials and Methods: Thirty one surgically treated patients with IOI between 1990 and 2015 were divided into sclerosing (SIOI) and non-sclerosing (NSIOI) to identify IgG4-ROD. Preserved pathological specimens were immunostained for IgG4 cells. Changes in clinical features were evaluated before and after treatment.Results: Out of the 31 patients, 15 (48.4%) had IgG4-ROD, consisting of 7 of the 16 SIOI (43.8%) and 8 of the 15 NSIOI patients (53.3%). Among 15 patients with IgG4-ROD, 4 (26.7%) achieved complete remission, which was significantly less than among IgG4-unrelated patients (11/16, 68.8%, p = .03). Furthermore, 3 out of 15 IgG4-ROD patients (20%) experienced recurrence, all of whom had SIOI, compared to 0% among IgG4-unrelated patients (p = .1).Conclusions: IgG4-ROD is common among previously identified IOI in our study. Treatment response is modest in IgG4-ROD patients.

Clinicopathologic Characterization of GREB1-rearranged Uterine Sarcomas With Variable Sex-Cord Differentiation.

Uterine mesenchymal tumors are genetically heterogenous; those with uniform cytomorphology, best exemplified by endometrial stromal tumors, often contain various fusion genes. Novel fusions involving ESR1 and GREB1, key factors in sex hormone pathways, have been implicated in rare uterine mesenchymal tumors. Particularly, the fusions between 5'-ESR1/GREB1 and 3'-NCOA2/NCOA3 were recently identified in 4 uterine tumors resembling ovarian sex-cord tumor (UTROSCT). By RNA sequencing, pathology review, and FISH screening, we identified 4 uterine sarcomas harboring rearranged GREB1, including GREB1-NCOA2 and the novel GREB1-NR4A3, GREB1-SS18, and GREB1-NCOA1, validated by RT-PCR and/or FISH. They occurred in the myometrium of postmenopausal women and were pathologically similar despite minor differences. Tumor cells were generally uniform and epithelioid, with vesicular nuclei and distinct to prominent nucleoli. Growth patterns included solid sheets, trabeculae/cords, nests, and fascicles. Only 1 tumor showed small foci of definitive sex-cord components featuring well-formed tubules, retiform structures, Leydig-like cells, and lipid-laden cells and exhibiting convincing immunoreactivity to sex-cord markers (calretinin, α-inhibin, and Melan-A). In contrast, all the 4 classic UTROSCT we collected occurred in premenopausal patients, consisted predominantly of unequivocal sex-cord elements, prominently expressed multiple sex-cord markers, and harbored ESR1-NCOA3 fusion. Combined with previously reported cases, GREB1-rearranged tumors involved significantly older women (P=0.001), tended to be larger and more mitotically active, showed more variable and often inconspicuous sex-cord differentiation, and appeared to behave more aggressively than ESR1-rearranged UTROSCT. Therefore, these 2 groups of tumors might deserve separate consideration, despite some overlapping features and the possibility of belonging to the same disease spectrum.

Developing a Prognostic Gene Panel of Epithelial Ovarian Cancer Patients by a Machine Learning Model.

Epithelial ovarian cancer patients usually relapse after primary management. We utilized the support vector machine algorithm to develop a model for the chemo-response using the Cancer Cell Line Encyclopedia (CCLE) and validated the model in The Cancer Genome Atlas (TCGA) and the GSE9891 dataset. Finally, we evaluated the feasibility of the model using ovarian cancer patients from our institute. The 10-gene predictive model demonstrated that the high response group had a longer recurrence-free survival (RFS) (log-rank test, p = 0.015 for TCGA, p = 0.013 for GSE9891 and p = 0.039 for NTUH) and overall survival (OS) (log-rank test, p = 0.002 for TCGA and p = 0.016 for NTUH). In a multivariate Cox hazard regression model, the predictive model (HR: 0.644, 95% CI: 0.436⁻0.952, p = 0.027) and residual tumor size < 1 cm (HR: 0.312, 95% CI: 0.170⁻0.573, p < 0.001) were significant factors for recurrence. The predictive model (HR: 0.511, 95% CI: 0.334⁻0.783, p = 0.002) and residual tumor size < 1 cm (HR: 0.252, 95% CI: 0.128⁻0.496, p < 0.001) were still significant factors for death. In conclusion, the patients of high response group stratified by the model had good response and favourable prognosis, whereas for the patients of medium to low response groups, introduction of other drugs or clinical trials might be beneficial.

Clear Cell Carcinoma of the Abdominal Wall as a Rare Complication of General Obstetric and Gynecologic Surgeries: 15 Years of Experience at a Large Academic Institution.

The objective of this article was to report the clinicopathological characteristics, treatment modalities, and outcomes of patients with clear cell carcinoma (CCC) of the abdominal wall. Medical records of six patients diagnosed with CCC of the abdominal wall between May 2003 and May 2018 at the National Taiwan University Hospital were reviewed. All patients had prior obstetric or gynecologic surgeries. The primary clinical presentation was enlarging abdominal masses at previous surgical scars. Four patients underwent initial/primary surgeries with/without adjuvant chemotherapy. One patient received neoadjuvant chemotherapy followed by surgical intervention and adjuvant chemotherapy, the other received chemotherapy and sequential radiotherapy without any surgical intervention. Two of four patients undergoing initial/primary surgeries had disease recurrence and the remaining two cases without initial surgery experienced disease progression during primary treatment. Inguinal lymph nodes were the most frequent sites of recurrence. In conclusion, previous obstetric or gynecologic surgery can be a risk factor for CCC of the abdominal wall. Complete resection of abdominal wall tumor and suspected intra-abdominal lesions with hysterectomy and bilateral inguinal lymph nodes dissection may be the primary treatment. Adjuvant chemotherapy would be considered for potential benefits. For patients without bilateral inguinal lymph nodes dissection, careful inguinal lymph node palpation during postoperative surveillance is necessary. More cases are still needed to elucidate the clinical management of this disease.

Long-term outcomes of surgical treatment for intravascular leiomyomatosis.

BACKGROUND: Intravascular leiomyomatosis (IVL) is relatively rare. The optimal surgical method and long-term outcomes are not completely understood. METHODS: Medical records between 2007 and 2017 in our hospital were analyzed to identify IVL cases with surgical intervention. Their medical records, operative details, and follow-up were collected by chart review and telephone communication. RESULTS: Eight patients with IVL were included in the study, accounting for 0.26% of all uterine leiomyoma cases. Primary IVL was confined to pelvic cavity in three patients, extended to the inferior vena cava (IVC) below renal vein in one, reached IVC and right atrium in three, and reached main pulmonary artery in one. One-stage operation was performed for seven patients. Cardiopulmonary bypass was done in four patients, and aortic cross-clamp and temporary circulatory arrest was performed in two patients. None of the four patients with intrapulmonary tumors received concomitant pulmonary tumor resection. There was no operative mortality and four morbidities, including ureter injury (2), bladder injury (1), and femoral vein thrombosis (1). During follow-up, two patients exhibited local recurrence of the tumor in the pelvis, and one patient had rapidly growing intrapulmonary tumor three months post-operatively. Intrapulmonary tumors in the other three patients remained stationary at 6, 84, and 120 months post-operatively. CONCLUSION: One-stage operation to completely remove IVL is feasible and with good long-term outcomes, which is recommended if the patient can tolerate the operation. Concomitant intrapulmonary tumors can be followed up watchfully except when associated with pleural effusion or the pathology indicating trend of increasing malignancy.

Outbreak of Microsporidial Keratoconjunctivitis Associated With Water Contamination in Swimming Pools in Taiwan.

PURPOSE: To report an outbreak of microsporidial keratoconjunctivitis resulting from a swimming pool in Taiwan. DESIGN: Retrospective case series. METHODS: The records of 13 teenagers (15 eyes) contracting microsporidial keratoconjunctivitis after swimming in a local swimming pool were reviewed. Corneal scrapings were collected in all eyes at a tertiary referred hospital in June 2017. Gram stain, modified Kinyoun acid-fast stain, polymerase chain reaction (PCR), and gene analysis of the microsporidian 16S ribosomal RNA (rRNA) were examined in all 15 cases. RESULTS: Symptoms occurred 1-12 days after the water contact. At presentation, all eyes showed nonpurulent conjunctivitis and small, plaque-like epithelial lesions peripherally (n = 6), centrally (n = 3), both peripherally and centrally (n = 5), or centrally with superficial punctate keratopathy (n = 1). During the follow-up period, 10 eyes developed central superficial punctate keratopathy (n = 6) or subepithelial haze or infiltrates, which were distributed centrally (n = 2) or peripherally (n = 3), following development of plaque-like epithelial lesions. The results of Gram stain and modified Kinyoun's acid-fast stain were confirmatory in 10 cases (67%). All 15 cases yielded positive PCR results and were all identified to be Vittaforma corneae. All followed-up eyes healed without sequelae using topical levofloxacin and betamethasone eye drops. CONCLUSIONS: Microsporidial keratoconjunctivitis can develop from contact with swimming pool water. The clinical course initially manifested as rapidly resolving conjunctivitis and peripheral plaque-like epithelial lesions, followed by paracentral or central plaque-like epithelial lesions, which evolved into subepithelial haze or infiltrates.

RBFOX3/NeuN is dispensable for visual function.

RBFOX3/NeuN is a neuronal splicing regulator involved in neural circuitry balance, as well as neurogenesis and synaptogenesis. Rbfox3 is expressed in neurons; however, in the retina, expression is restricted to cells in the ganglion cell layer and some cells of the inner nuclear layer. Rbfox3 is expressed in a layer-specific manner in the retina, which implies a functional role, however, the role of RBFOX3 in the retina is unknown. Rbfox3 homozygous knockout (Rbfox3-/-) mice exhibit deficits in visual learning; therefore, understanding the role of RBFOX3 in the retina is critical for interpreting behavioral results. We found Rbfox3 expression was developmentally regulated in the retina and specifically expressed in ganglion cells, amacrine cells and horizontal cells of the retina. We demonstrate deletion of Rbfox3 resulted in a reduction in the thickness of the inner plexiform layer of the retina, where synapses are formed. Number of ganglion cells and amacrine cells is normal with loss of Rbfox3. Innervation of retinal ganglion cells into their targeted brain regions is normal in Rbfox3-/- mice. Importantly, Rbfox3-/- mice displayed normal non-image and image forming functions. Taken together, our results suggest RBFOX3 is dispensable for visual function.

Using Ion Torrent sequencing to study genetic mutation profiles of fatal thyroid cancers.

BACKGROUND/PURPOSE: Surgery followed by radioiodine is a mainstay of treatment for thyroid cancers of follicular origins. However, about 5% of the thyroid cancers are non-operable and/or radioiodine-refractory diseases, which are either locally advanced or metastatic and result in a survival of less than 5 years. How to treat this population of thyroid cancer patients becomes a critical issue requiring further understanding of the tumor's genetic information. METHODS: We used formalin-fixed paraffin-embedded specimens of 22 fatal thyroid cancers and their corresponding non-tumor parts, if available, to yield genomic DNA, and applied the Ion Torrent™ Personal Genome Machine (IT-PGM) System (Life Technologies), a next generation sequencing technology, to interrogate 740 mutational hotspots in 46 oncogenes. We further validated the results by conventional direct sequencing. RESULTS: We confirmed 21 mutations of 11 oncogenes in the 22 fatal thyroid cancer samples. Among them, the MET p.N375S and MLH1 p.V384D mutations, each was detected in two cases, and has rarely been found to be involved in thyroid cancer pathogenesis before. We also identified homozygous PDGFRA p.V824V mutation in eight out of the 22 cases, while the non-tumor counterparts carried heterozygous PDGFRA p.V824V mutation. We noted that the Ion Torrent technique unfortunately showed high false positive rates for detecting EGFR mutations in thyroid cancers. CONCLUSION: The extensive genetic studies provide new insights to future targeted therapy in these patients. IT-PGM proved to be valuable for comprehensively searching genetic mutations in potentially fatal thyroid cancers.